DES-induced primary pituitary tumors in the ove F-344 rat continue to be studied in terms of prolactin cell heterogeneity as well as heterogeneity of PRL molecules contained within the mammotroph subtypes. We have been able to show by Western blotting that there are eight variant forms on 15% native gels, 13% on SDS-PAGE, and 6% on SDS-PAGE under reducing conditions. The biological (B)/immunological (I) activities of these variant forms are very different, both in intracellular and secreted forms. Interestingly, these variants may be specifically associated with separate mammotroph subpopulations. By reverse plaque assay, we have demonstrated that the small cells are primarily responsible for most of the hormone secretion in vitro. We also continue working on the source, identification, and mechanism of action of a rat serum PIF. The material is a high molecular weight protein, may come from formed elements, and inhibits synthesis of new PRL molecules very quickly. This material may indicate the presence of a new feedback regulatory system controlling PRL secretion from the mammalian pituitary. (C)